Development and activities, including immunocomplex formation, of biparatopic antibodies and alternative scaffold proteins

Abstract

Biparatopic antibodies and biparatopic alternative scaffolds are proteins that can simultaneously bind two distinct epitopes, and as such are promising formats for the development of next-generation antibody therapeutics. By design, biparatopic proteins have high avidity and can bridge between epitopes in an intra- or intermolecular manner to form diverse immunocomplexes. Some biparatopic proteins can be efficiently internalized into cells, which may be useful for the targeted delivery of therapeutic molecules into cells. In addition, biparatopic proteins can also lock the conformation of membrane proteins to exert an agonist or antagonist effect. Here, we review the development and characteristics of biparatopic proteins and examine how they differ in terms of antigen-binding efficiency, immunocomplex formation and biological activity compared with conventional monoparatopic proteins.